title: Contribution of endogenous glucagon-like peptide 1 to glucose metabolism after Roux-en-Y gastric bypass.
abstract: The contribution of elevated glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism after Roux-en-Y gastric bypass (RYGB) has been the subject of uncertainty. We used exendin-9,39, a competitive antagonist of GLP-1, to examine glucose metabolism, islet hormone secretion, and gastrointestinal transit in subjects after RYGB and in matched control subjects. Subjects were studied in the presence or absence of exendin-9,39 infused at 300 pmol/kg/min. Exendin-9,39 resulted in an increase in integrated postprandial glucose concentrations post-RYGB (3.6 ± 0.5 vs. 2.0 ± 0.4 mol/6 h, P = 0.001). Exendin-9,39 decreased insulin concentrations (12.3 ± 2.2 vs. 18.1 ± 3.1 nmol/6 h, P = 0.002) and the β-cell response to glucose (Total, 13 ± 1 vs. 11 ± 1 × 10(-9) min(-1), P = 0.01) but did not alter the disposition index (DI). In control subjects, exendin-9,39 also increased glucose (2.2 ± 0.4 vs. 1.7 ± 0.3 mol/6 h, P = 0.03) without accompanying changes in insulin concentrations, resulting in an impaired DI. Post-RYGB, acceleration of stomach emptying during the first 30 min by exendin-9,39 did not alter meal appearance, and similarly, suppression of glucose production and stimulation of glucose disappearance were unaltered in RYGB subjects. These data indicate that endogenous GLP-1 has effects on glucose metabolism and on gastrointestinal motility years after RYGB. However, it remains uncertain whether this explains all of the changes after RYGB.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic College of Medicine, Rochester, MN.
authors.forename: Meera
authors.initials: M
authors.lastname: Shah
authors.forename: Jennie H
authors.initials: JH
authors.lastname: Law
authors.forename: Francesco
authors.initials: F
authors.lastname: Micheletto
authors.forename: Matheni
authors.initials: M
authors.lastname: Sathananthan
authors.forename: Chiara
authors.initials: C
authors.lastname: Dalla Man
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rizza
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
mesh_terms: D016022:Case-Control Studies; D005260:Female; D015390:Gastric Bypass; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D005947:Glucose